We plan to continue our efforts in regard to dissecting immunopathological mechanisms of virus infection, with emphasis on effector mechanisms, particularly natural killer (NK) cells, and on viral regulation mchanisms, with emphasis on defective interfering (DI) virus. Specifically, we plan (a) to examine surface sialic acid and glycolipid structure on target cells with varied sensitivities to NK cell, before and after interferon treatment, (b) to determine whether NK cells are efficient mediators of antiviral ADCC in the mouse system, using LCMV, HSV, Sindbis, MHV, and Sendai virus infected L-929 cells, (c) to develop and utilize in vivo cytotoxicity assays to examine the effects of defective interfering (DI) LCMV on protecting cells from immunosurveillance, as we have shown in vitro (Welsh and Oldstone, 1977). 125IUDR-labeled L-929 cells under various conditions of standard and DI virus infection will be injected intravenously into C3H/St mice, and the fate of the cells in vivo examined.